Effect of Automated Insulin Delivery on Early-stage Diabetic Complications

Type 1 Diabetes Clinical Trial

— AID-Comp  

Official title:

Effect of Automated Insulin Delivery With Advanced Closed-loop on Glucose Outcomes and Early-stage Diabetic Complications

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05477030
• Other study ID #: 2022004
• Status: Recruiting
• Phase: N/A
• Start date: February 23, 2022
• Est. completion date: February 23, 2024

Study information

• Verified date: July 2022
• Source: University of Milan
• Contact: Elio Ippolito, MS
• Phone: 0239042648
• Email: elio.ippolito[@]unimi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim of this study is to verify the effects of an advanced HCL (Medtronic Minimed™ 780G) compared to SAP with PLGS on metabolic outcomes and markers of early microvascular damage in a population of adults with T1D previously treated with CSII. Evaluation of endothelial disfunction and autonomic neuropathy will also be performed.

Description:

New algorithms for the automation of insulin delivery (AID) are showing great benefit on glucose control in people with type 1 diabetes. Indeed, Hybrid closed loop (HCL) systems can improve HbA1c levels, percentage of time in defined glucose range, time below range and time over range, according to RCT and observational studies results. However, scientific evidences demonstrating potential benefits on the reduction of diabetes complications are limited regarding CSII or SAP with demonstrated reduction of cardiovascular mortality, improvement of albuminuria and peripheral nerve damage.

Data on AID effects on complications of diabetes are missing. In this study intermediate damage markers will be measured to assess potential effects of AID in comparison to sensor augmented pumps.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: February 23, 2024
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female patients

• T1D patients above 18 years in CSII treatment for at least 3 months

• HbA1c values between 6.0% and 9.5%

• Disease duration = 2 years

• Written informed consent obtained from the patient

Exclusion Criteria:

• Pregnancy

• Participation to other clinical trials

• A history of alcohol or drug abuse

• Advanced diabetic nephropathy defined as presence of albuminuria = 300 mg/g or eGFR < 60 ml/min/1,73m2

• Proliferative Diabetic retinopathy or macular edema

• Established Atherosclerotic Cardiovascular Disease (ASCVD) or history of heart failure

• Presence of serious diseases or conditions which in the opinion of the Investigator makes patient non-eligible for the study

• Hypoglycemia Unawareness (Clarke score > 4)

• Patients unable to understand spoken and written Italian language

Related Conditions & MeSH terms

• Diabetes Complications
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Device:
• Medtronic MiniMed 780G with SmartGuard activation
Insulin pump implemented with alghoritm for automatic modulation of insulin delivery (to increase time in glucose range 70-180 mg/dl)
• Medtronic MiniMed 780G without SmartGuard activation
Insulin pump implemented with alghoritm for low glucose insulin suspension (to reduce hypoglycemia rate)

Locations

Country	Name	City	State
Italy	ASST FBF Sacco	Milan

Sponsors (1)

Lead Sponsor	Collaborator
University of Milan

Country where clinical trial is conducted

Italy, 

References & Publications (25)

Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, Dovc K, Doyle FJ 3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, Jia W, Kor — View Citation

Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. — View Citation

Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce C, Perkins BA, Welsh JB, Willi SM, Wood MA; STAR 3 Study Group. Sensor-augmented pump therapy for A1C reduction (STAR 3) study: results from the 6-month continuation phase. Diabete — View Citation

Bott U, Mühlhauser I, Overmann H, Berger M. Validation of a diabetes-specific quality-of-life scale for patients with type 1 diabetes. Diabetes Care. 1998 May;21(5):757-69. — View Citation

Clarke WL, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W. Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care. 1995 Apr;18(4):517-22. — View Citation

Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insuli — View Citation

EQuality1 Study Group--Evaluation of QUALITY of Life and Costs in Diabetes Type 1, Nicolucci A, Maione A, Franciosi M, Amoretti R, Busetto E, Capani F, Bruttomesso D, Di Bartolo P, Girelli A, Leonetti F, Morviducci L, Ponzi P, Vitacolonna E. Quality of li — View Citation

Fiorina P, La Rocca E, Venturini M, Minicucci F, Fermo I, Paroni R, D'Angelo A, Sblendido M, Di Carlo V, Cristallo M, Del Maschio A, Pozza G, Secchi A. Effects of kidney-pancreas transplantation on atherosclerotic risk factors and endothelial function in — View Citation

Forlenza GP, Li Z, Buckingham BA, Pinsker JE, Cengiz E, Wadwa RP, Ekhlaspour L, Church MM, Weinzimer SA, Jost E, Marcal T, Andre C, Carria L, Swanson V, Lum JW, Kollman C, Woodall W, Beck RW. Predictive Low-Glucose Suspend Reduces Hypoglycemia in Adults, — View Citation

Garg SK, Weinzimer SA, Tamborlane WV, Buckingham BA, Bode BW, Bailey TS, Brazg RL, Ilany J, Slover RH, Anderson SM, Bergenstal RM, Grosman B, Roy A, Cordero TL, Shin J, Lee SW, Kaufman FR. Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insu — View Citation

Lepore G, Scaranna C, Corsi A, Dodesini AR, Trevisan R. Switching from Suspend-Before-Low Insulin Pump Technology to a Hybrid Closed-Loop System Improves Glucose Control and Reduces Glucose Variability: A Retrospective Observational Case-Control Study. Di — View Citation

Maniatis AK, Toig SR, Klingensmith GJ, Fay-Itzkowitz E, Chase HP. Life with continuous subcutaneous insulin infusion (CSII) therapy: child and parental perspectives and predictors of metabolic control. Pediatr Diabetes. 2001 Jun;2(2):51-7. — View Citation

Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and c — View Citation

Nimri R, Muller I, Atlas E, Miller S, Fogel A, Bratina N, Kordonouri O, Battelino T, Danne T, Phillip M. MD-Logic overnight control for 6 weeks of home use in patients with type 1 diabetes: randomized crossover trial. Diabetes Care. 2014 Nov;37(11):3025-3 — View Citation

Pankowska E, Blazik M, Dziechciarz P, Szypowska A, Szajewska H. Continuous subcutaneous insulin infusion vs. multiple daily injections in children with type 1 diabetes: a systematic review and meta-analysis of randomized control trials. Pediatr Diabetes. — View Citation

Pettus JH, Zhou FL, Shepherd L, Preblick R, Hunt PR, Paranjape S, Miller KM, Edelman SV. Incidences of Severe Hypoglycemia and Diabetic Ketoacidosis and Prevalence of Microvascular Complications Stratified by Age and Glycemic Control in U.S. Adult Patient — View Citation

Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med. 2008 Jul;25(7):765-74. doi: 10.1111/j.1464-5491.200 — View Citation

Polonsky WH, Fisher L, Earles J, Dudl RJ, Lees J, Mullan J, Jackson RA. Assessing psychosocial distress in diabetes: development of the diabetes distress scale. Diabetes Care. 2005 Mar;28(3):626-31. — View Citation

Rosenlund S, Hansen TW, Andersen S, Rossing P. Effect of 4 years subcutaneous insulin infusion treatment on albuminuria, kidney function and HbA1c compared with multiple daily injections: a longitudinal follow-up study. Diabet Med. 2015 Nov;32(11):1445-52 — View Citation

Rosenlund S, Hansen TW, Rossing P, Andersen S. Effect of Sensor-Augmented Pump Treatment Versus Multiple Daily Injections on Albuminuria: A 1-Year Randomized Study. J Clin Endocrinol Metab. 2015 Nov;100(11):4181-8. doi: 10.1210/jc.2015-2839. Epub 2015 Sep — View Citation

Salehi P, Roberts AJ, Kim GJ. Efficacy and Safety of Real-Life Usage of MiniMed 670G Automode in Children with Type 1 Diabetes Less than 7 Years Old. Diabetes Technol Ther. 2019 Aug;21(8):448-451. doi: 10.1089/dia.2019.0123. Epub 2019 Jun 5. — View Citation

Steineck I, Cederholm J, Eliasson B, Rawshani A, Eeg-Olofsson K, Svensson AM, Zethelius B, Avdic T, Landin-Olsson M, Jendle J, Gudbjörnsdóttir S; Swedish National Diabetes Register. Insulin pump therapy, multiple daily injections, and cardiovascular morta — View Citation

Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002 May 15;287(19):25 — View Citation

Zabeen B, Craig ME, Virk SA, Pryke A, Chan AK, Cho YH, Benitez-Aguirre PZ, Hing S, Donaghue KC. Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality. PLoS One. 2016 Apr 6;11(4):e0153033. doi: 10.1371/journal. — View Citation

Zoppini G, Bergamini C, Trombetta M, Sabbagh L, Dauriz M, Mantovani A, Targher G, Fossà I, Rinaldi E, Bonora E. Increased aortic stiffness index in patients with type 1 diabetes without cardiovascular disease compared to controls. J Endocrinol Invest. 201 — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time in glycemic range 70-180 mg/dl	time spent by the patient in glucose range	From Baseline to 26 weeks
Primary	Glycated Hemoglobin (HbA1c)	percentage of hemoglobin glycosylated	From Baseline to 26 weeks
Secondary	Early microangiopathic damage markers: sTNFR-1/2	sTNFR-1/2 (pg/ml)	From Baseline to 26 weeks
Secondary	Early microangiopathic damage markers: B-2 microglobulin	B-2 microglobulin (pg/ml)	From Baseline to 26 weeks
Secondary	Early microangiopathic damage markers: cystatin C	cystatin C (ng/ml)	From Baseline to 26 weeks
Secondary	Early microangiopathic damage markers: neutrophil gelatinase-associated lipocalin	neutrophil gelatinase-associated lipocalin (ng/ml)	From Baseline to 26 weeks
Secondary	Early microangiopathic damage markers: osteopontin	osteopontin (pg/ml)	From Baseline to 26 weeks
Secondary	Early microangiopathic damage markers: vWF levels	vWF levels (ng/ml)	From Baseline to 26 weeks
Secondary	Endothelial disfunction	Endothelial-dependent dilation (EDD) is considered a marker of dysfunctional abnormalities involved in early phases of atherosclerosis development. Changes in EDD precede structural changes and occurs in the preclinical phase of vascular disease.; In the present study endothelial dependent dilation is assessed by color Doppler evaluation of flow increase after hyperemia.	From Baseline to 26 weeks